Naotaka Iwamoto

Global diffuse distribution in the brain and efficient gene delivery to the dorsal root ganglia by intrathecal injection of adeno-associated viral vector serotype 1

The success of gene therapy for inherited neurodegenerative diseases such as metachromatic leukodystrophy (MLD) depends on the development of efficient gene delivery throughout the brain guarded by the blood–brain barrier and achieves distribution of the deficient enzyme throughout the brain. Direct injection of viral vector into the brain parenchyma is too invasive and may not be sufficient to treat the entire brain. As an alternative approach, we examined the feasibility of intrathecal (IT) injection of adeno‐associated viral vector serotype 1 (AAV1).

Treatment of low back pain in patients with vertebral compression fractures and superior cluneal nerve entrapment neuropathies

Background: Superior cluneal nerve entrapment neuropathy (SCN-EN) may contribute to low back pain (LBP). However, it is often misdiagnosed as lumbar spine disorder and poorly understood. Methods: Between April 2012 and September 2013, we treated 27 patients (3 men, 24 women; mean age 75.0 years) with LBP due to SCN-EN elicited by vertebral compression fractures. Symptoms were unilateral in 4 patients and bilateral in 23 patients. The interval between symptom onset and treatment averaged 10.8 months; the mean postoperative follow-up period was 19.0 months. The clinical outcomes were assessed utilizing the numeric rating scale (NRS) for LBP, the Japanese Orthopedic Association (JOA) score, and the Roland–Morris Disability Questionnaire (RDQ) before and after treatment (e.g., until the latest follow-up). Results: LBP in 17 patients was immediately improved by SCN block only. The remaining 10 patients required surgery (involving 18 sites) as SCN blocks were only transiently effective. Operative intervention resulted in the immediate and continued improvement of their LBP. Notably, their NRS decreased from 7.4 to 1.5, their RDQ scores from 19.6 to 7.0, and their JOA scores increased from 10.7 to 20.3. Conclusions: In this series, 27 patients with LBP due to SCN-EN responded either to SCN blocks (17 patients) or surgical release of SCN entrapment (10 patients at 18 sites).

Microsurgical Decompression for Peroneal Nerve Entrapment Neuropathy.

Peroneal nerve entrapment neuropathy (PNEN) is one cause of numbness and pain in the lateral lower thigh and instep, and of motor weakness of the extensors of the toes and ankle. We report a less invasive surgical procedure performed under local anesthesia to treat PNEN and our preliminary outcomes. We treated 22 patients (33 legs), 7 men and 15 women, whose average age was 66 years. The mean postoperative follow-up period was 40 months. All patients complained of pain or paresthesia of the lateral aspect of affected lower thigh and instep; all manifested a Tinel-like sign at the entrapment point. As all had undergone unsuccessful conservative treatment, we performed microsurgical decompression under local anesthesia. Of 19 patients who had undergone lumbar spinal surgery (LSS), 9 suffered residual symptoms attributable to PNEN. While complete symptom abatement was obtained in the other 10 they later developed PNEN-induced new symptoms. Motor weakness of the extensors of the toes and ankle [manual muscle testing (MMT) 4/5] was observed preoperatively in 8 patients; it was relieved by microsurgical decompression. Based on self-assessments, all 22 patients were satisfied with the results of surgery. PNEN should be considered as a possible differential diagnosis in patients with L5 neuropathy due to lumbar degenerative disease, and as a causative factor of residual symptoms after LSS. PNEN can be successfully addressed by less-invasive surgery performed under local anesthesia.

Low Back Pain Caused by Superior Cluneal Nerve Entrapment Neuropathy in Patients with Parkinson Disease

n patients with Parkinson disease (PD), postural abnormalities and increased muscle tonus lead to musculoskeletal I problems. The incidence of such problems was significantly higher in patients with PD than in an age-matched control group comprising patients with stroke and brain tumor. Low back pain (LBP) in particular was reported more frequently by patients with PD; in approximately 50%, it negatively affected their quality of life and activities of daily living (ADL). It is difficult to treat LBP in patients with PD, and the results of surgery to address their spinal diseases are unsatisfactory.

Long-term Outcome of Surgical Treatment for Superior Cluneal Nerve Entrapment Neuropathy

Study Design. Prospective observational cohort study. Objective. The objective of this study was to present the long-term surgical outcomes of operative treatment for superior cluneal nerve (SCN) entrapment neuropathy (SCNEN) and to analyze the causes of poor results and further treatment required. Summary of Background Data. There are a few reports of the outcomes of surgical treatment for SCNEN, and most studies describe results for operations conducted under general anesthesia with short follow-up periods. Methods. Surgery was performed for SCNEN in 52 consecutive patients on 79 sides, excluding patients who had undergone previous surgery on the lumbar spine. Entrapment was unilateral in 25 patients and bilateral in 27. The mean postoperative follow-up period was 41.3 months (range, 29–58 months). All patients had received conservative treatment without improvements, and operations were performed under local anesthesia. Results. Twenty-three cases (44%) involved only low-back pain (LBP), and 31 cases (60%) involved LBP associated with leg numbness or pain. The mean number of SCN branches decompressed in the operative field at the first operation was 1.4 (range, 1–4 branches). There were no local or systemic complications during or after the operation. All patients reported symptom improvement, but LBP caused by SCNEN recurrence was reported for 10 sides (13%) in seven patients who subsequently underwent repeat surgery. In the second surgery, the number of additionally treated SCN branches was 2.0 (range, 1–5). Additional surgeries were performed in two cases for lumbar disorders. All patients showed significant improvement at the last follow-up visit (P < 0.05), including those who developed recurrence. Conclusion. Long-term outcomes of surgical treatment for SCNEN were satisfactory. For prevention of recurrence, as many SCN branches as possible should be decompressed in the operation field during the first operation. Level of Evidence: 4

The impact of atherosclerotic factors on cerebral aneurysm is location dependent: aneurysms in stroke patients and healthy controls.

Previous studies have indicated that cerebrovascular diseases (CVDs) seem to increase the occurrence of unruptured intracranial aneurysms (UIAs). However, this maybe explained by the fact that CVDs and UIAs share common risk factors, such as hypertension (HT) and smoking. To clarify the impact of atherosclerotic risk factors on cerebral aneurysmal formation, we explored the incidence of UIAs and their locations in healthy controls and patients with CVD, who frequently have atherosclerotic risk factors. This study included consecutive 283 asymptomatic healthy adults and 173 acute stroke patients, from patients diagnosed with acute cerebral hemorrhage or cerebral infarction and admitted to our hospital. The incidence, maximum diameter, and location of UIAs were evaluated, and we also investigated the following factors: age, gender, current smoking, HT, diabetes mellitus (DM), and dyslipidemia. UIAs were found in 19 of the total 456 subjects (4.2%), 11 of 283 healthy subjects (3.9%), and 8 of 173 stroke patients (4.6%). These differences are not statically significant. The incidence of middle cerebral artery (MCA) aneurysms was significantly higher in the CVD patients than in the healthy controls (P = .03), and the incidence of paraclinoid aneurysms was significantly higher in the healthy controls than in the CVD patients (P = .03). Moreover, higher incidences of HTs and CVDs in the MCA aneurysms than in the other locations of UIAs were observed. These results indicate that the impact of atherosclerotic factors on cerebral aneurysmal formation depends on their location and that there is a stronger impact on MCA aneurysms than on paraclinoid aneurysms.

Supratentorial extraventricular anaplastic ependymoma in an adult with repeated intratumoral hemorrhage

We report the case of a 61-year-old man with supratentorial extraventricular anaplastic ependymoma who presented with repeated intratumoral hemorrhage. The patient was admitted with headache. Computed tomography and magnetic resonance imaging showed an enhancing mass with intratumoral hemorrhage in the right temporal lobe. Gross total resection was performed. The tumor was well demarcated from the brain tissue, and showed no continuity with the ventricular system. Histopathological examination revealed the features of anaplastic ependymoma. Therefore, additional radiation therapy and adjuvant chemotherapy were administered. Ten months later, the tumor recurred with hemorrhage in the spinal canal. This case showed rapid malignant progression and repeated intratumoral hemorrhage within a short period of time, both of which are characteristics of anaplastic ependymomas. Close observation of the central nervous system and adjuvant radiotherapy are mandatory, even if the ependymoma presents with repeated intratumoral hemorrhage.

Common diseases mimicking lumbar disc herniation and their treatment

1Department of Neurosurgery, Chiba Hokuso Hospital, Nippon Medical School, Inzai-city, Chiba 270-1694, Japan. 2Department of Neurosurgery, Kushiro Rosai Hospital, Kushiro-city, Hokkaido 085-0088, Japan. 3Department of Neurosurgery, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan. 4Department of Neurosurgery, Teikyo University, Itabashi-ku, Tokyo 173-8606, Japan. 5Department of Neurosurgery, Iwate Medical University, Morioka-city, Iwate 020-8505, Japan.

Repetitive Plantar Flexion Test as an Adjunct Tool for the Diagnosis of Common Peroneal Nerve Entrapment Neuropathy

OBJECTIVE The diagnosis of common peroneal nerve entrapment neuropathy (CPNEN) is based on clinical symptoms and nerve conduction studies. However, nerve conduction studies may not detect abnormalities. Under the hypothesis that repetitive plantar flexion that loads the peroneal nerve (PN) at the entrapment point without lumbar loading would be a useful CPNEN provocation test, we evaluated the repetitive plantar flexion (RPF) test as an adjunct diagnostic tool for CPNEN. The study design was a retrospective analysis of prospectively collected data. METHODS Our study population consisted of 18 consecutive patients whose ipsilateral CPNEN improved significantly after PN neurolysis. Using repetitive ankle plantar flexion as a CPNEN provocation test, results were recorded as positive when it elicited numbness and/or pain in the affected area of the PN. RESULTS The RPF test induced symptoms on all affected sides in the course of 57.4 seconds (range, 14-120 seconds). In 3 patients it induced numbness in the affected area of the PN in the normal leg. Receiver operating characteristic analysis showed that the diagnostic sensitivity and accuracy of the test were 94.4% each. The suggested cutoff point was 110 seconds and the area under the receiver operating characteristic curve was 0.97 (95% confidence interval 0.93-1.02). The positive and the negative predictive values were 89.5% and 94.1%, respectively. CONCLUSIONS Our simple RPF test elicited the symptoms of CPNEN and our provocation test helped to identify dynamic PN entrapment neuropathy as the origin of intermittent claudication.

Surgical treatment of middle cluneal nerve entrapment neuropathy: technical note

OBJECTIVE The etiology of low-back pain (LBP) is heterogeneous and is unknown in some patients with chronic pain. Superior cluneal nerve entrapment has been proposed as a causative factor, and some patients suffer severe symptoms. The middle cluneal nerve (MCN) is also implicated in the elicitation of LBP, and its clinical course and etiology remain unclear. The authors report the preliminary outcomes of a less invasive microsurgical release procedure to address MCN entrapment (MCN-E). METHODS The authors enrolled 11 patients (13 sites) with intractable LBP judged to be due to MCN-E. The group included 3 men and 8 women ranging in age from 52 to 86 years. Microscopic MCN neurolysis was performed under local anesthesia with the patient in the prone position. Postoperatively, all patients were allowed to walk freely with no restrictions. The mean follow-up period was 10.5 months. LBP severity was evaluated on the numerical rating scale (NRS) and by the Japanese Orthopaedic Association (JOA) and the Roland-Morris Disability Questionnaire (RDQ) scores. RESULTS All patients suffered buttock pain, and 9 also had leg symptoms. The symptoms were aggravated by standing, lumbar flexion, rolling over, prolonged sitting, and especially by walking. The numbers of nerve branches addressed during MCN neurolysis were 1 in 9 patients, 2 in 1 patient, and 3 in 1 patient. One patient required reoperation due to insufficient decompression originally. There were no local or systemic complications during or after surgery. Postoperatively, the symptoms of all patients improved statistically significantly; the mean NRS score fell from 7.0 to 1.4, the mean RDQ from 10.8 to 1.4, and the mean JOA score rose from 13.7 to 23.6. CONCLUSIONS Less invasive MCN neurolysis performed under local anesthesia is useful for LBP caused by MCN-E. In patients with intractable LBP, MCN-E should be considered.